Alemtuzumab Overview

Introduction of Alemtuzumab

Alemtuzumab is a humanized anti-CD52 IgG1 monoclonal antibody that depletes CD52-expressing cells from the circulation. This drug (marketed as Campath, MabCampath or Campath-1H and currently under further development as Lemtrada) is a monoclonal antibody used in the treatment of chronic lymphocytic leukemia (CLL), cutaneous T-cell lymphoma (CTCL) and T-cell lymphoma. It was approved by the US Food and Drug Administration for CLL patients who have been treated with alkylating agents and who have failed fludarabine therapy. Since the approval of the US Food and Drug Administration (FDA) in November 2014, alemtuzumab is approved in over 30 countries for the therapy of relapsing-remitting multiple sclerosis (RRMS). Alemtuzumab demonstrated superiority to subcutaneous (sc) interferon β-1a (IFNβ-1a), an established disease-modifying therapy (DMT) for RRMS. The high efficacy of alemtuzumab, with remarkable effects on clinical and radiological disease outcome parameters is offset by frequent and significant adverse events. Besides infusion-associated reactions (IAR), mild to moderate infections, especially the occurrence of secondary autoimmune disease, has somewhat dampened enthusiasm for alemtuzumab. Approximately 30%-40% of patients develop secondary autoimmune diseases predominantly affecting thyroid, kidney and thrombocytic function.

Mechanism of Action of Alemtuzumab

CD52 is a 21-28 kDa cell surface glycoprotein attached to the cell membrane by a glycosylphosphatidyl-inositol anchor of 12 amino acids. CD52 is one of the most abundant membrane glycoproteins on T and B lymphocytes and is also expressed on natural killer (NK) cells, monocytes, macrophages, dendritic cells, and eosinophilic granulocytes and to a lesser extent on neutrophilic granulocytes. CD52 is not expressed on erythrocytes, platelets, and hematopoietic progenitor cells. The exact function of CD52 is unknown but it is suggested that the molecule may be involved in T lymphocyte co-stimulation, the induction of regulatory T lymphocytes, and T lymphocyte migration and adhesion. Alemtuzumab is an IgG1 kappa with human variable framework and constant regions, and complementarity-determining regions derived from a rat monoclonal antibody. This agent selectively binds to CD52, thereby triggering a host immune response that results in lysis of CD52+ cells. In other words, alemtuzumab induces antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), and activates pro-apoptotic pathways on CD52-expressing cells. Administration of alemtuzumab causes a profound depletion of T and B lymphocytes, NK cells, dendritic cells, granulocytes, and monocytes by three mechanisms: complement-dependent cytotoxicity (through C1q activation and subsequent generation of the membrane attack complex), antibody-dependent cellular cytotoxicity (after the activation of NK cells and macrophages through their IgG fragment C receptor), and induction of apoptosis. Depletion of peripheral lymphocytes occurs within 1h after alemtuzumab administration. Lymphocyte depletion from secondary lymphoid tissues occurs over 3-5 days. Alemtuzumab administration significantly depletes peripheral monocytes and NK cells.

Mechanism of Action of Alemtuzumab

Fig 1. Mechanism of Action of Alemtuzumab

Table 1. Clinical Projects of Alemtuzumab*

NCT ID Status Conditions Lead Sponsor Update Time
NCT03302754 Recruiting Allogeneic Hematopoietic Cell Transplantation Children's Hospital Medical Center, Cincinnati October 5, 2017
NCT03135249 Recruiting Multiple Sclerosis (MS) University of Texas Southwestern Medical Center May 1, 2017
NCT03193086 Recruiting Multiple Sclerosis Glostrup University Hospital, Copenhagen June 20, 2017
NCT03477500 Recruiting Multiple Sclerosis Haukeland University Hospital March 26, 2018
NCT03784898 Recruiting Multiple Sclerosis Genzyme, a Sanofi Company December 24, 2018
NCT00858117 Active, not recruiting Leukemia Northwestern University March 9, 2009
NCT02689453 Recruiting T-Cell Lymphoma Relapsed, Adult T-Cell Leukemia (ATL), Peripheral T-Cell Lymphoma (PTCL), Cutaneous T Cell Lymphoma (CTCL), T-Cell Prolymphocytic Leukemia National Cancer Institute (NCI) February 24, 2016
NCT02419378 Recruiting Multiple Sclerosis, Relapsing-Remitting University Hospital Muenster April 17, 2015
NCT03774914 Recruiting Multiple Sclerosis Genzyme, a Sanofi Company December 13, 2018
NCT03368664 Recruiting Multiple Sclerosis Genzyme, a Sanofi Company December 11, 2017
NCT02385110 Recruiting Leukemia M.D. Anderson Cancer Center March 11, 2015
NCT03806387 Recruiting Multiple Sclerosis University of Aarhus January 16, 2019
NCT00069238 Active, not recruiting Lymphoma, T-Cell; Lymphoma, Extranodal NK-T-Cell National Cancer Institute (NCI) September 18, 2003
NCT02583594 Active, not recruiting Progressive Multiple Sclerosis Genzyme, a Sanofi Company October 22, 2015
NCT00345345 Active, not recruiting T-LGL Lymphoproliferative Disorders National Heart, Lung, and Blood Institute (NHLBI) June 28, 2006
NCT02472054 Recruiting Hemophagocytic Lymphohistiocytosis (HLH) Assistance Publique - Hôpitaux de Paris June 15, 2015
NCT01465334 Active, not recruiting CLL, SLL Dana-Farber Cancer Institute November 4, 2011
NCT01361711 Active, not recruiting Stage I Chronic Lymphocytic Leukemia, Stage II Chronic Lymphocytic Leukemia, Stage III Chronic Lymphocytic Leukemia, Stage IV Chronic Lymphocytic Leukemia Northwestern University May 27, 2011
NCT00195624 Active, not recruiting Severe Aplastic Anemia, Refractory; Severe Aplastic Anemia, Relapse National Heart, Lung, and Blood Institute (NHLBI) September 19, 2005
NCT01030900 Active, not recruiting Hodgkin Lymphoma, Diffuse Large B-Cell Lymphoma National Cancer Institute (NCI) December 14, 2009
NCT02255656 Active, not recruiting Relapsing Remitting Multiple Sclerosis Genzyme, a Sanofi Company October 2, 2014
NCT00040846 Active, not recruiting Leukemia Fred Hutchinson Cancer Research Center January 27, 2003
NCT03647722 Recruiting Multiple Sclerosis University of Southern California August 27, 2018
NCT02623946 Active, not recruiting Multiple Sclerosis Clinique Neuro-Outaouais December 8, 2015
NCT00553098 Active, not recruiting Immunodeficiency Syndrome, Non-Cancer Diagnosis Fred Hutchinson Cancer Research Center November 5, 2007
NCT01120028 Active, not recruiting Kidney Transplantation University of Oxford May 10, 2010
NCT03591380 Recruiting Kidney Transplantation University of Wisconsin, Madison July 19, 2018
NCT03250169 Recruiting Multiple Sclerosis Queen Mary University of London August 15, 2017
NCT03587272 Recruiting Sickle Cell Disease Allistair Abraham, MD July 16, 2018
NCT01729494 Active, not recruiting Renal Transplantation University of Cincinnati November 20, 2012
NCT03910452 Not yet recruiting Chronic Granulomatous Disease National Institute of Allergy and Infectious Diseases (NIAID) April 10, 2019
NCT00408447 Recruiting Sickle Cell Disease, Beta Thalassemia Columbia University December 7, 2006
NCT01659606 Recruiting Dyskeratosis Congenita, Hoyeraal Hreidarsson Syndrome, Revesz Syndrome, Aplastic Anemia Boston Children’s Hospital August 8, 2012
NCT03421756 Recruiting Sickle Cell Disease Kathleen Dorritie February 5, 2018
NCT03214354 Recruiting Sickle Cell Disease, Stem Cell Transplant Complications, Red Blood Cell Disorder, Pure Red Cell Aplasia University of Calgary July 11, 2017
NCT00920972 Recruiting Metabolic Disorders, Hematologic, Immune, or Bone Marrow Disorders, Hemoglobinopathies, Non-malignant Disorders Washington University School of Medicine June 16, 2009
NCT00565773 Active, not recruiting Organ Transplantation Emory University November 30, 2007
NCT00619528 Active, not recruiting Immunosuppression, Kidney Transplantation, Graft Rejection Northwestern University February 21, 2008
NCT01877837 Active, not recruiting Sickle Cell Disease Hackensack Meridian Health June 14, 2013
NCT01897688 Active, not recruiting Type 1 Diabetes, Severe Hypoglycemic Unawareness Northwestern University July 12, 2013
NCT02626715 Recruiting Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Hematopoietic Stem Cell Transplant (HSCT) Randy Windreich December 10, 2015
NCT01821781 Recruiting Immune Deficiency Disorders, Severe Combined Immunodeficiency, Chronic Granulomatous Disease, X-linked Agammaglobulinemia, Wiskott-Aldrich Syndrome, Hyper-IgM, DiGeorge Syndrome, Chediak-Higashi Syndrome, Common Variable Immune Deficiency, Immune Dysregulatory Disorders, Hemophagocytic Lymphohistiocytosis, IPEX, Autoimmune Lymphoproliferative Syndrome, X-linked Lymphoproliferative Syndrome Washington University School of Medicine April 1, 2013
NCT00426517 Recruiting Inherited Immune Deficiencies National Institute of Allergy and Infectious Diseases (NIAID) January 24, 2007
NCT03504241 Recruiting Kidney Transplantation, Renal Transplantation, Renal Transplant Recipient National Institute of Allergy and Infectious Diseases (NIAID) April 20, 2018
NCT01050855 Recruiting Non-Malignant Diseases, Immunodeficiencies, Hemoglobinopathies Children's Hospital of Philadelphia January 18, 2010
NCT01935128 Active, not recruiting Renal Transplant University of Toledo Health Science Campus September 4, 2013
NCT02867800 Recruiting Sickle Cell Disease, Graft Versus Host Disease Monica Bhatia August 16, 2016
NCT02435901 Active, not recruiting Sickle Cell Disease, Beta Thalassemia-Major Northwell Health May 6, 2015
NCT02678143 Recruiting Sickle Cell Disease Washington University School of Medicine February 9, 2016
NCT00061568 Recruiting Congenital Hemolytic Anemia, Sickle Cell Disease National Heart, Lung, and Blood Institute (NHLBI) May 29, 2003
NCT00368355 Recruiting Acute Lymphoblastic Leukemia, Non Hodgkins Lymphoma, Myelodysplastic Syndrome, Acute Myeloid Leukemia, Chronic Myelogenous Leukemia, Hemophagocytic Lymphohistiocytosis (HLH), Familial Hemophagocytic Lymphohistiocytosis (FLH), Viral-associated Hemophagocytic Syndrome (VAHS), X-linked Lymphoproliferative Disease (XLP) Baylor College of Medicine August 24, 2006
NCT01962415 Recruiting Primary Immunodeficiency (PID), Congenital Bone Marrow Failure Syndromes, Inherited Metabolic Disorders (IMD), Hereditary Anemias, Inflammatory Conditions Paul Szabolcs October 14, 2013
NCT02105766 Recruiting Sickle Cell Disease, Thalassemia, Stem Cell Transplantation, Graft vs Host Disease National Heart, Lung, and Blood Institute (NHLBI) April 7, 2014
NCT03821610 Recruiting Acute Lymphoblastic Leukemia University of Birmingham January 30, 2019
NCT00977691 Active, not recruiting Sickle Cell Anemia National Heart, Lung, and Blood Institute (NHLBI) September 16, 2009
NCT02038478 Recruiting Sickle Cell Disease and Thalassemia University of Texas Southwestern Medical Center January 16, 2014
NCT03535298 Recruiting Multiple Sclerosis, Relapsing-Remitting The Cleveland Clinic May 24, 2018
NCT03182426 Recruiting Diabetes Mellitus, Type 1 University of Alberta June 9, 2017
NCT03194321 Recruiting End Stage Renal Disease Cedars-Sinai Medical Center June 21, 2017
NCT02497404 Recruiting Leukemia, Erythroblastic, Acute, Myelodysplastic Syndromes Weill Medical College of Cornell University July 14, 2015
NCT00566696 Active, not recruiting Leukemia, Acute Lymphocytic (ALL); Leukemia, Myeloid, Acute(AML); Leukemia, Myeloid, Chronic(CML); Juvenile Myelomonocytic Leukemia (JMML); Hemoglobinuria, Paroxysmal Nocturnal (PNH); Hodgkin Lymphoma; Lymphoma, Non-Hodgkin (NHL); Myelodysplastic Syndrome (MDS) St. Jude Children's Research Hospital December 3, 2007
NCT01625351 Active, not recruiting Ewing Sarcoma, Gastrointestinal Tumor, Germ Cell Tumor, Hepatic Tumor, Lymphoma, Wilms Tumor, Rhabdoid Tumor, Clear Cell Carcinoma, Renal Cell Carcinoma, Melanoma, Neuroblastoma, Rhabdomyosarcoma, Non-rhabdomyosarcoma St. Jude Children's Research Hospital June 21, 2012
NCT02059239 Recruiting Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma Weill Medical College of Cornell University February 11, 2014
NCT02061800 Recruiting Chronic Myeloid Leukemia (CML), Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS), Juvenile Myelomonocytic Leukemia (JMML), Acute Lymphoblastic Leukemia (ALL), Lymphoma (Hodgkin's and Non-Hodgkin's) Diane George, MD February 13, 2014
NCT01256398 Active, not recruiting Acute Lymphoblastic Leukemia, Adult B Acute Lymphoblastic Leukemia With t (9;22) (q34.1; q11.2); BCR-ABL1, Untreated Adult Acute Lymphoblastic Leukemia National Cancer Institute (NCI) December 8, 2010
NCT00176852 Active, not recruiting Sickle Cell Disease, Thalassemia, Severe Congenital Neutropenia, Diamond-Blackfan Anemia, Shwachman-Diamond Syndrome Masonic Cancer Center, University of Minnesota September 15, 2005
NCT02162420 Recruiting Dyskeratosis Congenita, Aplastic Anemia Masonic Cancer Center, University of Minnesota June 12, 2014
NCT01652092 Recruiting SCID, Omenn's Syndrome, Reticular Dysgenesis, Wiskott-Aldrich Syndrome, Bare Lymphocyte Syndrome, Common Variable Immunodeficiency, Chronic Granulomatous Disease, CD40 Ligand Deficiency, Hyper IgM Syndrome, X-linked Lymphoproliferative Disease, Hemophagocytic Lymphohistiocytosis, Griscelli Syndrome, Chediak-Higashi Syndrome, Langerhan's Cell Histiocytosis Masonic Cancer Center, University of Minnesota July 27, 2012
NCT03630211 Recruiting Systemic Sclerosis, Diffuse Sclerosis Systemic, Interstitial Lung Disease, Pulmonary Hypertension Paul Szabolcs August 14, 2018
NCT01909245 Recruiting Type 1 Diabetes Mellitus City of Hope Medical Center July 26, 2013
NCT03500731 Recruiting Idiopathic Pulmonary Fibrosis, Emphysema or COPD Paul Szabolcs April 17, 2018
NCT03444064 Recruiting Diabetes, Diabetes Mellitus, Type 1 University of Alberta February 23, 2018
NCT03653338 Recruiting Sickle Cell Anemia, Beta-thalassemia Major, Diamond-blackfan Anemia Beth Carella, DO August 31, 2018
NCT00924170 Active, not recruiting Adult T-Cell Leukemia (ATL) National Cancer Institute (NCI) June 18, 2009
NCT03128996 Recruiting Severe Sickle Cell Disease, Bone Marrow Failure Syndromes, Metabolic Disorders, Immunologic Disorders, Hemoglobinopathies, Non-malignant Disorders Washington University School of Medicine April 26, 2017
NCT03784547 Not yet recruiting Multiple Sclerosis Hospital Italiano de Buenos Aires December 24, 2018
NCT01240525 Active, not recruiting Graft Versus Host Disease, Leukemia, Lymphoma, Myeloma, Myelodysplastic Syndrome University College, London November 15, 2010
NCT01247701 Active, not recruiting Myeloid Hematological Malignancies Baylor College of Medicine November 24, 2010
NCT01013441 Active, not recruiting Chronic Lymphocytic Leukemia University of Pennsylvania November 13, 2009
NCT00692939 Recruiting Crohn's Disease Paul Szabolcs June 6, 2008
NCT01966367 Recruiting Bone Marrow Failure Syndrome, Severe Aplastic Anemia, Severe Congenital Neutropenia, Amegakaryocytic Thrombocytopenia, Diamond-Blackfan Anemia, Schwachman Diamond Syndrome, Primary Immunodeficiency Syndromes, Acquired Immunodeficiency Syndromes, Histiocytic Syndrome, Familial Hemophagocytic Lymphocytosis, Lymphohistiocytosis, Macrophage Activation Syndrome, Langerhans Cell Histiocytosis (LCH), Hemoglobinopathies, Sickle Cell Disease, Sickle Cell-beta-thalassemia Diane George, MD October 21, 2013
NCT01889381 Recruiting Facial Injuries, Traumatic Wounds and Injuries, Craniofacial Injuries, Craniofacial Defects Johns Hopkins University June 28, 2013
NCT01862965 Active, not recruiting Chronic Graft-versus-host Disease Universitätsklinikum Hamburg-Eppendorf May 27, 2013
NCT02179359 Recruiting Sickle Cell Disease, Transfusion Dependent Alpha- or Beta-, Thalassemia, Diamond Blackfan Anemia, Paroxysmal Nocturnal Hemoglobinuria, Glanzmann Thrombasthenia, Severe Congenital Neutropenia, Shwachman-Diamond Syndrome, Non-Malignant Hematologic Disorders Masonic Cancer Center, University of Minnesota July 1, 2014
NCT02629120 Recruiting X-Linked Chronic Granulomatious Disease National Institute of Allergy and Infectious Diseases (NIAID) December 14, 2015
NCT03500328 Recruiting Multiple Sclerosis, Relapsing-Remitting Johns Hopkins University April 17, 2018
NCT01459107 Recruiting Amputation, Traumatic, Wounds and Injuries, Hand Injuries Johns Hopkins University October 25, 2011
NCT01949129 Recruiting Acute Lymphoblastic Leukaemia St. Anna Kinderkrebsforschung September 24, 2013
NCT03077542 Enrolling by invitation Sickle Cell Disease National Heart, Lung, and Blood Institute (NHLBI) March 13, 2017
NCT03193866 Recruiting Relapsing-remitting Multiple Sclerosis Karolinska Institutet June 21, 2017
NCT00889798 Active, not recruiting Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM) iOMEDICO AG April 29, 2009
NCT02171104 Recruiting Metabolic Disorders Masonic Cancer Center, University of Minnesota June 23, 2014
NCT03444805 Not yet recruiting Autoimmune Diseases European Group for Blood and Marrow Transplantation February 23, 2018
NCT03836690 Not yet recruiting Lymphoma, Leukemia, Myeloma, Myelodysplastic Syndromes Severe Aplastic Anemia, Primary Immune Deficiency, Graft Vs Host Disease University College, London February 11, 2019

Table 2. Approved Drugs of Alemtuzumab**

INN (trade name) Therapeutic area Dose Strength Route Company Marketing start Market
Compath B-cell chronic lymphocytic leukemia VIAL 10MG/ML Intravenous Genzyme June 23, 2000 Overview
Lemtrada Relapsing forms of multiple sclerosis (MS) Injection 12MG/1.2ML Intravenous infusion Genzyme September 17, 2017 Overview

What We Provide

Therapeutic Antibody

We provide high-quality (IgG1 - kappa type) for use in FuncS, IF, Neut, ELISA, FC, IP, ICC and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

Reference
*The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?term=Alemtuzumab

**Information presented in the table were collected from the following website:
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=103948

Send Inquiry

  • Verification code
    Click image to refresh the verification code.
© 2007 - 2019 Creative BioLabs All Rights Reserved
  • 0
  • 0

Cart